The goal of this project is to analyze glutamate (GLU) and aspartate (ASP) chemosensitivity in cultured hippocampal neurons. Specific aims include: 1. Mimicking the action of the natural synaptic transmitter with brief pulses of GLU and ASP. 2. Determining if hippocampal neurons have discrete regions of high GLU and ASP sensitivity. 3. Correlating areas of sensitivity with presynaptic terminals. 4. Correlating regions of GLU and ASP sensitivity. 5. Blocking synaptic transmission with GLU and ASP antagonists. 6. Determining channel lifetime, reversal potential, and conductance for GLU and ASP. 7. Showing that the channel affected by synaptic transmitter has the same properties as the channel opened by GLU and ASP. The experiments will be done with dissociated rat hippocapal neurons maintained in tissue culture. The physiology experiments will involve standard intracellular recording or patch clamp recording done under direct visual control. The long-term objectives of this project are directed toward providing rigorous physiological and pharmacological evidence that GLU and possibly ASP are used as excitatory transmitters in the mammalian central nervous system. The most obvious clinical impact of this knowledge would be in neuropharmacology, where it could stimulate the development of more potent and selective antagonists of GLU or ASP. These antagonists would have great potential in treating epilepsy and movement disorders and could be useful as sedatives, hypnotics, and anesthetics.